This invention relates to a process for the preparation of an improved mutant strain of Bordetella bronchiseptica having strong immunogenicity and low virulence, which is suitable for the preparation of B. bronchiseptica live attenuated vaccines. The present invention also relates to a live vaccine prepared from B. bronchiseptica.
Bordetella bronchiseptica has been known to cause respiratory disease in various animals such as swine, dogs, rabbits, guinea pigs and mice. Infection with the organisms in neonatal pigs causes swine atrophic rhinitis (hereinafter designated as AR) which induces nasal turbinate atrophy and results in growth delay and a decrease of the feed consumption ratio. This is a serious problem in the livestock industry. A killed AR vaccine has been commercialized for the prophylaxis of swine AR; however, the effectiveness of the vaccine is limited.
Recently, a live attenuated AR vaccine was developed and reported by Shimizu et al. (U.S. Pat. No. 4,456,588). However, the organisms involved in this live vaccine can grow only at 34.degree.-37.degree. C. Also, these organisms are slow to form colonies on a solid medium and show poor colonization on the nasal mucosa of swine, and also show no serum antibody production when inoculated in pigs.
At least 10-14 days are necessary to obtain the immunologic effects of killed AR vaccine after administration. Therefore, a vaccine with strong immunity at an early infant stage has long been sought. B. bronchiseptica has generally been known to grow at 32.degree.-37.degree. C. ("Atrophic Rhinitis of Swine Bordetella Infectious Disease", Ed. M. Ogata, Buneido Publ. Co., 1979). And the fact that pathogenic bacteria lose their virulence, when cultured at a high temperature, is also known.
In order to obtain mutant strains of B. bronchiseptica for the production of live AR vaccine, we have considered the above phenomena, and have devised the present invention which includes a process for the preparation of an improved mutant strain of B. bronchiseptica having strong immunity and low virulence, and a live attenuated AR vaccine prepared therefrom.